Evidence map›Paper›PMID 25549049›Full record

ArticleEndocrinology2015

Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

Nicole E Cyr, Jennifer S Steger, Anika M Toorie, Jonathan Z Yang, Ronald Stuart, Eduardo A Nillni

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 37 citations in OpenAlex.

  1. Animals : an open access journal from MDPI · 2025
    Article
  2. Article
  3. Review
  4. The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022
    Review
  5. Article
  6. Article
  7. Exploring the Genetic Conception of Obesity via the Dual Role of FoxO.International journal of molecular sciences · 2021
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Advances in TRH signaling.Reviews in endocrine & metabolic disorders · 2016
    Review
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Nicole E CyrDivision of Endocrinology (N.E.C., J.S.S., A.M.T., J.Z.Y., R.S., E.A.N.), Department of Medicine, The Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island 02903; and Department of Molecular Biology, Cell Biology, and Biochemistry (E.A.N.), Brown University, Providence, Rhode Island 02912.
Jennifer S Steger
Anika M Toorie
Jonathan Z Yang
Ronald Stuart
Eduardo A Nillni
Brown University · USRhode Island Hospital · US

Funding

Hypothalamic SIRT1 and Energy BalanceR01DK085916 · NIDDK · RHODE ISLAND HOSPITAL · PI NILLNI, EDUARDO A. · 2010 to 2013
$1.4M
NIDDK NIH HHS DK085916SNIDDK NIH HHS R01 DK085916
6 · The paper itself

Abstract

In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

Indexed as

alpha-MSHAnimalsBody WeightCarboxypeptidase HDietary FatsEnergy MetabolismForkhead Box Protein O1Forkhead Transcription FactorsGene Expression Regulation, EnzymologicMaleNerve Tissue ProteinsObesityPro-OpiomelanocortinRatsRats, Sprague-DawleySirtuin 1alpha-MSHCarboxypeptidase HDietary FatsForkhead Box Protein O1Forkhead Transcription FactorsFoxo1 protein, ratNerve Tissue ProteinsPro-OpiomelanocortinSirt1 protein, ratSirtuin 1

Identifiers

PMID25549049
PMCPMC4330311
OpenAlexW2121618285

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.